Altered endothelin receptor expression in prehepatic portal hypertension predisposes the liver to microcirculatory dysfunction in rats

Background/Aims: Endothelin (ET) is one of the most active vascular regulators in the liver. It is unknown how partial portal vein ligation (PPVL) induced prehepatic portal hypertension influences the response of the liver to ET and its agonists. Therefore, this study was conducted to determine the expression of ET receptors and its functional significance after PPVL. Methods: Competitive receptor binding study and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) were performed using liver homogenates after 2 weeks of PPVL or sham operation in rats. Hepatic microcirculation was evaluated in vivo using intravital microscopy. Results: Although there was no significant difference in dissociation constant (K_d) and total amount of receptors (B_max) between sham and PPVL, the proportion of ET_B receptor was significantly increased in PPVL. RT-PCR analysis confirmed the up-regulation of ET_B receptors demonstrated by the competitive receptor binding assay. In the functional study, infusion of ET_B agonist (IRL 1620) in a low dosage did not change the hepatic microcirculation in sham but strongly constricted the sinusoids leading to a reduction of sinusoidal perfusion in PPVL. Conclusions: These results suggest that prehepatic portal hypertension may predispose the hepatic microcirculation to dysregulation in stress conditions where ET is upregulated.